tbuckley/cabot-search huggingface dataset:
Improvements in Adverse Event Rates Among Hospitalized Patients
Authors: Noel Eldridge
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Association of Cigarette Smoking and Alcohol Consumption With Subsequent Mortality Among Black Breast Cancer Survivors in New Jersey
Authors: Nur Zeinomar, Bo Qin, Saber Amin, Yong Lin, Baichen Xu, Dhanya Chanumolu, Coral O. Omene, Karen S. Pawlish, Kitaw Demissie, Christine B. Ambrosone, Chi-Chen Hong, Elisa V. Bandera
Journal: JAMA Network Open (2023)

Importance There are limited data about how lifestyle factors are associated with breast cancer prognosis among Black or African American women because most of the evidence is based on studies of White breast cancer survivors. Objective To examine the association of prediagnostic cigarette smoking and alcohol consumption with all-cause mortality and breast cancer–specific mortality in a cohort of Black breast cancer survivors. Design, Setting, and Participants This population-based cohort study included 1926 Black or African American breast cancer survivors who received a diagnosis from June 6, 2005, to May 21, 2019, identified in 10 counties in New Jersey through rapid case ascertainment by the New Jersey State Cancer Registry. Statistical analysis was conducted from January 1, 2021, to August 1, 2022. Exposures Information on prediagnostic cigarette smoking, alcohol consumption, and additional covariates was collected during in-person interviews. The covariates examined included smoking status at the time of breast cancer diagnosis (currently smoking at the time of breast cancer diagnosis, formerly smoking, or never smoking), smoking duration (number of years smoking), smoking intensity (cigarettes smoked per day), number of pack-years of smoking, and regular alcohol consumption the year before diagnosis (categorized as nondrinkers, ≤3 drinks per week, or &amp;amp;gt;3 drinks per week). Main Outcomes and Measures Primary outcomes included breast cancer–specific mortality and all-cause mortality. Results Among the 1926 women in the study, the mean (SD) age at breast cancer diagnosis was 54.4 (10.8) years. During 13 464 person-years of follow-up (median follow-up, 6.7 years [range, 0.5-16.0 years]), there were 337 deaths, of which 187 (55.5%) were breast cancer related. Compared with never smokers, current smokers at the time of breast cancer diagnosis had a 52% increased risk for all-cause mortality (hazard ratio [HR], 1.52; 95% CI, 1.15-2.02), which was most pronounced for those with 10 or more pack-years of smoking (HR, 1.84; 95% CI, 1.34-2.53). Similar findings were observed for breast cancer–specific mortality (current smokers vs never smokers: HR, 1.27; 95% CI, 0.87-1.85), although they were not statistically significant. There was no statistically significant association between alcohol consumption and all-cause mortality (&amp;amp;gt;3 drinks per week vs nondrinkers: HR, 1.05; 95% CI, 0.73-1.51) or breast cancer–specific mortality (&amp;amp;gt;3 drinks per week vs nondrinkers: HR, 1.06; 95% CI, 0.67-1.67). Conclusions and Relevance This population-based cohort study of Black breast cancer survivors suggests that current smoking at the time of diagnosis was associated with an increased risk of all-cause mortality, particularly among women with greater pack-years of smoking.
Risk of COVID-19 Diagnosis and Hospitalisation in Patients with Osteoarthritis or Back Pain Treated with Ibuprofen Compared to Other NSAIDs or Paracetamol: A Network Cohort Study
Authors: Junqing Xie, James T. Brash, Cigdem Turkmen, Stefan Driessen, Giustino Varrassi, George Argyriou, Sarah Seager, Christian Reich, Daniel Prieto-Alhambra
Journal: Drugs (2023)

We aimed to investigate whether ibuprofen use, compared with other non-selective non-steroidal anti-inflammatory drugs (ns-NSAIDs), cyclooxygenase-2 inhibitors (COX-2i) or paracetamol, increases the risk of coronavirus disease 2019 (COVID-19) diagnosis or hospitalisation. A prevalent user and active comparator cohort study. Two US claims databases (Open Claims and PharMetrics Plus) mapped to the Observational Medical Outcomes Partnership Common Data Model. Insured patients with a history of osteoarthritis or back pain and receiving ibuprofen, other ns-NSAIDs, COX-2i or paracetamol between 1 November, 2019 and 31 January, 2020 (study enrolment window 1) or between 1 February, 2020 and 31 October, 2020 (study enrolment window 2). Large-scale propensity score matching and empirical calibration were used to minimise confounding. Incidence and hazard ratios of COVID-19 diagnosis and hospitalisation according to drug/s use were estimated and pooled in the same study period across data sources using a fixed-effects meta-analysis. Index treatment episode was the primary risk evaluation window, censored at the time of discontinuation. A total of 633,562 and 1,063,960 participants were included in periods 1 and 2, respectively, for the ibuprofen versus ns-NSAIDs comparison, 311,669 and 524,470 for ibuprofen versus COX-2i, and 492,002 and 878,598 for ibuprofen versus paracetamol. Meta-analyses of empirically calibrated hazard ratios revealed no significantly differential risk of COVID-19 outcomes in users of ibuprofen versus any of the other studied analgesic classes: hazard ratios were 1.13 (0.96–1.33) for the ibuprofen-ns-NSAIDs comparison, 1.03 (0.83–1.28) for the ibuprofen-COX-2i comparison and 1.13 (0.74–1.73) for ibuprofen-paracetamol comparison on COVID-19 diagnosis in the February 2020–October 2020 window. Similar hazard ratios were found on COVID-19 hospitalisation and across both study periods. In patients with osteoarthritis or back pain, we found no differential risks of incident COVID-19 diagnosis or COVID-19 hospitalisation for ibuprofen users compared with other ns-NSAIDs, COX-2i or paracetamol. Our findings support regulatory recommendations that NSAIDs, including ibuprofen, should be prescribed as indicated in the same way as before the COVID-19 pandemic, especially for those who rely on ibuprofen or NSAIDs to manage chronic arthritis or musculoskeletal pain symptoms.
Medical Costs of Substance Use Disorders in the US Employer-Sponsored Insurance Population
Authors: Mengyao Li, Cora Peterson, Likang Xu, Christina A. Mikosz, Feijun Luo
Journal: JAMA Network Open (2023)

Direct costs of substance use disorders (SUDs) in the United States are incurred primarily among the working-age population. Quantifying the medical cost of SUDs in the employer-sponsored insurance (ESI) population can improve understanding of how SUDs are affecting workplaces and inform decision-making on the value of prevention strategies.To estimate the annual attributable medical cost of SUDs in the ESI population from the health care payer perspective.In this economic evaluation, Merative MarketScan 2018 databases were weighted to represent the non-Medicare eligible ESI population. Regression and mathematical modeling of medical expenditures controlled for insurance enrollee demographic, clinical, and insurance factors to compare enrollees with and without an SUD diagnosis to identify the annual attributable medical cost of SUDs. Data analysis was conducted from January to March 2022.International Statistical Classification of Diseases, Tenth Revision, Clinical Modification SUD diagnoses on inpatient or outpatient medical records according to Clinical Classifications Software categories (alcohol-, cannabis-, hallucinogen-, inhalant-, opioid-, sedative-, stimulant-, and other substance-related disorders).Annual SUD medical cost in the ESI population overall and by substance type (eg, alcohol). Number of enrollees with an SUD diagnosis and the annual mean cost per affected enrollee of SUD diagnosis (any and by substance type) are also reported.Among 162 million ESI enrollees, 2.3 million (1.4%) had an SUD diagnosis in 2018. The regression analysis sample included 210 225 individuals with an SUD diagnosis (121 357 [57.7%] male individuals; 68 325 [32.5%] aged 25-44 years) and 1 049 539 individuals with no SUD diagnosis. The mean annual medical cost attributable to SUD diagnosis per affected enrollee was $15 640 (95% CI, $15 340-$15 940), and the total annual medical cost in the ESI population was $35.3 billion (2018 USD). Alcohol use disorder ($10.2 billion) and opioid use disorder ($7.3 billion) were the most costly.In this economic evaluation of medical expenditures in the ESI population, the per-person and total medical costs of SUDs were substantial. Strategies to support employees and their health insurance dependents to prevent and treat SUDs can be considered in terms of potentially offsetting the existing high medical cost of SUDs. Medical expenditures for SUDs represent the minimum direct cost that employers and health insurers face because not all people with SUDs have a diagnosis, and costs related to absenteeism, presenteeism, job retention, and mortality are not addressed.
FXYD3 enhances IL-17A signaling to promote psoriasis by competitively binding TRAF3 in keratinocytes
Authors: Wenjuan Yang, Rukun He, Hao Qu, Wenwen Lian, Yue Xue, Tao Wang, Wenlong Lin, Peishuo Zhu, Meng Xia, Lihua Lai, Qingqing Wang
Journal: Cellular and Molecular Immunology (2023)
Targeting Pim kinases in hematological cancers: molecular and clinical review
Authors: Marcia Bellon, Christophe Nicot
Journal: Molecular Cancer (2023)

Abstract Decades of research has recognized a solid role for Pim kinases in lymphoproliferative disorders. Often up-regulated following JAK/STAT and tyrosine kinase receptor signaling, Pim kinases regulate cell proliferation, survival, metabolism, cellular trafficking and signaling. Targeting Pim kinases represents an interesting approach since knock-down of Pim kinases leads to non-fatal phenotypes in vivo suggesting clinical inhibition of Pim may have less side effects. In addition, the ATP binding site offers unique characteristics that can be used for the development of small inhibitors targeting one or all Pim isoforms. This review takes a closer look at Pim kinase expression and involvement in hematopoietic cancers. Current and past clinical trials and in vitro characterization of Pim kinase inhibitors are examined and future directions are discussed. Current studies suggest that Pim kinase inhibition may be most valuable when accompanied by multi-drug targeting therapy.
Phase 2 trial of pembrolizumab (pembro) and bavituximab (bavi) in advanced hepatocellular carcinoma (HCC).
Authors: David Hsieh, Radhika Kainthla, Hao Zhu, Muhammad S. Beg
Journal: Journal of Clinical Oncology (2023)

584 Background: Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and is responsible for more than 500,000 deaths annually. Bavi, a monoclonal antibody designed to inhibit the immunosuppressive effects of phosphatidylserine through interaction with TIM and TAM receptor family members in the tumor microenvironment (TME), is being evaluated in combination with pembro, a monoclonal antibody designed to inhibit Programmed cell death protein 1 (PD-1), in patients with advanced HCC. Methods: This phase 2, open-label, multi-site trial included patients with histologically confirmed locally advanced or metastatic HCC who have not received prior systemic therapy. Patients were treated with pembro (200 mg Q3W) in combination with bavi (3 mg/kg QW) until disease progression. The primary endpoint of the trial is confirmed ORR by RECIST 1.1. A minimax two-stage method to analyze ORR after 15 patients and enroll an additional 13 patient if 3 or more responses observed in first 15 patients (NCT03519997). Results: Three out of 15 evaluable patients responded during Stage 1, allowing for enrollment to continue with a planned 13 additional patients in Stage 2. The study completed enrollment after a total of 28 patients were determined to be evaluable. The confirmed ORR based upon data from 28 patients evaluable for response was 32% (9 confirmed, partial responses). The disease control rate was 61% (9 partial responses, 8 stable disease). The safety profile of pembro plus bavi was consistent with the established profiles of individual drugs and updated adverse events will be reported at the time of presentation along with correlative studies. Conclusions: The combination of bavi and pembro appears to be well tolerated in this patient population and has a toxicity profile comparable to monotherapy immune checkpoint inhibitor. Preliminary analyses suggests that bavi and pembro may have promising anti-tumor activity in advanced HCC. Clinical trial information: NCT03519997 .
Exploring real-world outcomes with nivolumab plus chemotherapy in patients with advanced gastroesophageal adenocarcinoma.
Authors: Clara Chen, Ying Zhang, Min You, Eleni Theodorou, David Bertwistle
Journal: Journal of Clinical Oncology (2023)

325 Background: In the pivotal CheckMate-649 trial, nivolumab in combination with chemotherapy (nivo + chemo), compared with chemotherapy alone (chemo), demonstrated superior efficacy in patients with previously untreated, advanced gastric, gastro-esophageal junction, or esophageal adenocarcinoma (collectively: gastroesophageal adenocarcinoma). This study aimed to describe the real-world patterns of use and effectiveness of nivo + chemo for first-line (1L) treatment of advanced gastroesophageal adenocarcinoma. Methods: Patients aged ≥18 years, newly diagnosed with unresectable, advanced or metastatic, HER2-negative gastroesophageal adenocarcinoma, who received nivo + chemo or chemo only between 4/1/2021 and 5/31/2022 were identified from the Flatiron Health database. Chemo regimens included FOLFOX or CAPEOX. Patients were followed from index date (start of 1L therapy) until death, loss of data availability, or end of data abstraction (05/31/2022), whichever occurred first. Results: 352 patients with advanced or metastatic gastroesophageal adenocarcinoma were eligible for the analysis (N=158 in the nivo + chemo group and N=194 in the chemo group). Baseline demographic and clinical characteristics were balanced between groups. Median follow-up was 3.6 (interquartile range [IRQ]: 1.5–8.1) months for nivo + chemo and 4.4 (IQR: 1.9–7.6) months for chemo. 44.3% of patients in the nivo + chemo group and 36.1% in the chemo group had &lt;3 months of follow-up available. Median overall survival (OS) from index date was not reached (95% confidence interval [CI]: 9.0 months, –) in the nivo + chemo group and was 10.0 (95% CI: 8.5, 11.6) months in the chemo group. 43 patients (27.2%) in the nivo + chemo group died during the study period compared with 64 patients (33.0%) in the chemo group. Median progression-free survival (PFS) from index date in patients who received nivo + chemo was 6.9 (95% CI: 5.6, 8.2) months compared to 5.5 (95% CI: 4.8, 7.4) months in patients who received chemo. Similar trends were observed in the subgroup of patients with a PD L1 combined positive score (CPS) ≥1, while data on the CPS ≥5 subgroup were not mature enough for meaningful analyses. Conclusions: The addition of nivolumab to chemotherapy for 1L treatment of advanced or metastatic gastroesophageal adenocarcinoma showed a trend towards survival benefit in the real-world setting. The study is ongoing. Subsequent analyses will capture a larger patient sample and longer follow-up, and describe PD L1 CPS-based subgroups. [Table: see text]
Treatment patterns and oncologic outcomes of carcinoma of the ampulla of vater in a reference hospital in a middle income country: A real-world–based study.
Authors: Abdel Karim Dip Borunda, Ricardo Jesus Arteaga Garcia, Javier Barragan Los Santos, Rafael Medrano Guzman, Alvaro Leal Sosa, Alfonso Pimentel
Journal: Journal of Clinical Oncology (2023)

524 Background: Gallbladder and other biliary tract tumors account for 0.6 % of all cancers. There is scarce data of Ampullary cancers, but it is known as an extremely rare neoplasia accounting just for 0.2% of gastrointestinal cancers and 7% of periampullary tumors. Most frequent histology is adenocarcinoma being intestinal and pancreatobiliary subtypes conditioning prognosis and treatment. Current approaches include, but not limited to: neo/adyuvant, radiation and palliative therapy. Methods: We conducted a retrospective study in a referral specialized center in Mexico city. We included patients with histologically confirmed ampullary cancer treated between 2008 and 2022, stages I-IV. We evaluated the frequency of surgery, radiation therapy and chemotherapy. Also, we registered, first line, subsequent and maintenance therapy and as for radiation and chemoradiation. Chi square and student T test were used for between group comparisons. Overall survival was performed using the Kaplan Meier method. Results: We included 220 patients with a median age of 60.3 years (range 28-84), female 51.8%. The clinical stage distribution was I 10%, II 16.4%, III 41.3%, IV 32.3%. Performance status 0 (26.5%), 1 (44.5%), 2 (15.6%), 3 (10.4%), 4 (2.8%). Histologic Subtype Adenocarcinoma not otherwise specified 45.7%, Intestinal Adenocarcinoma 27.1%, Pancreatobiliary Adenocarcinoma 16.7%, Mix Intestinal-Pancreatobiliary 6.2%, Signet Ring Cell Adenocarcinoma 2.4%, Neuroendocrine 1.9%. Curative intend surgery in 169 patients was possible in 90%. Initial treatment received was Adjuvant 40.9%, Palliative 27.7%, Neoadjuvant 2.3% and Never Received any kind of treatment in 29.1%. Adjuvant Treatment was given to 94 patients. Among them Gemcitabine and Capecitabine was the election of treatment in 34% and 23.4 respectively. First line Treatment. Patients receiving first line treatment (110 patients) were candidates to Gemcitabine, XELOX, and Gemcitabine-Cisplatin in 30%, 13.6% and 12.7% according to physicians and 56% other line of treatment. Patients who progressed to first line received a second line in 19%. Most frequent second line of treatment was Capecitabine 61.9% and Gemcitabine 23.8%. Of the whole population Median Overall Survival was 30.68 months, Disease Free survival: 30.71 months and 8.0 months for progression free survival in first line. Conclusions: To our knowledge first real world based large volume study reporting treatment patterns and oncologic outcomes of a rare entity.
Randomized phase 2 study of DKN-01 plus FOLFIRI/FOLFOX and bevacizumab versus FOLFIRI/FOLFOX and bevacizumab as second-line treatment of advanced colorectal cancer (DeFianCe).
Authors: Zev A. Wainberg, Ralph V. Boccia, John H Strickler, Markus H. Moehler, Cynthia A. Sirard, Erin K Walsh, Elizabeth C Parker, Keun-Wook Lee
Journal: Journal of Clinical Oncology (2023)

TPS275 Background: Colorectal cancer is the third most prevalent cancer, and the prognosis of patients with advanced metastatic (mCRC) is poor. The efficacy of standard of care (SOC) second-line chemotherapy combinations with anti-vascular endothelial growth factor (VEGF) therapies remains modest. Previously treated advanced mCRC that is microsatellite stable (MSS/pMMR) represents nearly 95% of the metastatic population and remains a high unmet medical need. DKN-01 is a humanized IgG4 monoclonal antibody (mAb) targeted against Dickkopf-related protein 1 (DKK1), a regulator of the Wnt signaling pathway. DKK1 has been identified as a potential oncogenic driver in CRC and has been correlated with 5FU resistance. Therefore, DKK1 expression is a potential predictive biomarker for chemotherapeutic resistance in CRC. Methods: This is a phase 2 randomized, open-label, two-part, multicenter study with a safety run-in to evaluate safety and efficacy of DKN-01 plus FOLFIRI/FOLFOX and bevacizumab versus SOC [FOLFIRI/FOLFOX and bevacizumab] as second-line treatment of advanced mCRC patients. In Parts A and B, approximately 150 advanced MSS, BRAF Wild Type mCRC patients with radiographic progression during or following 1 prior line of systemic treatment will be enrolled in the study. Part A is a safety run-in with DKN-01 plus FOLFIRI/FOLFOX and bevacizumab in at least 20 safety evaluable patients. In Part B, approximately 130 patients will be randomized 1:1 to either the experimental (DKN-01 plus FOLFIRI/FOLFOX and bevacizumab) or control arm (FOLFIRI/FOLFOX and bevacizumab), using a central stratified block randomization scheme and stratified based on DKK1 RNAscope tumor percentage score (TPS) (≥1% vs &lt;1%). Primary endpoint is progression free survival and secondary endpoints include overall response rate, duration of response, overall survival and incidence of ≥Grade 3 related treatment-related adverse events (TRAEs). Exploratory endpoints will include evaluation of efficacy outcomes based upon tumoral DKK1 expression. Recruitment is ongoing. Clinical trial information: NCT05480306 .
Racial and regional disparities in the management of locally advanced rectal cancer.
Authors: William Yu Luo, Chris B Agala, Pragna Shetty, Muneera Rehana Kapadia, Jonathan Michael Stem, Jose G. Guillem
Journal: Journal of Clinical Oncology (2023)

14 Background: Surgical margins following rectal cancer resection impact oncologic outcomes and may reflect adequacy of care. We examined the relationship between race, ethnicity, or region of care with margin positivity following rectal cancer resection. Methods: We queried the National Cancer Database (NCDB) for patients diagnosed with stage II-IV rectal cancer between 2004-2018 who underwent surgical resection and excluded patients with missing data for race/ethnicity and radiation therapy/surgery status, and/or who had local excision only. We performed a propensity-score analysis via inverse probability of treatment weighting (IPTW) of margin positivity rate as outcome and race/ethnicity and region as predictors of interest. We controlled for age, sex, Charlson-Deyo Score, pathologic stage, pathologic grade, time from diagnosis to surgical resection, surgery type, sequence of radiation and surgery, facility type, insurance type, level of education, distance between patient and facility, and region of the United States. Results: Our query yielded 73,269 patients. Median patient age was 63 (IQR: 54-72) years and 40% were female. 81%,8%, 6%, and 5% were non-Hispanic White, non-Hispanic Black, Hispanic, and non-Hispanic Other, respectively. After IPTW adjustment, non-Hispanic Black patients had 19% higher odds of margin positivity relative to non-Hispanic White patients (OR: 1.185, 95% CI: 1.094-1.284; p&lt;.0001) Patients in the Northeast United States had a 10% lower odds of margin positivity compared to those in the South (OR: 0.900, 95% CI: 0.842-0.962; p=0.0019). Conclusions: Being non-Hispanic Black was significantly associated with a higher likelihood of positive margin following rectal cancer resection when compared to their non-Hispanic White counterparts. Patients in the South also experienced significantly higher rates of positive margin when compared to Northeast patients. Further investigation into potential interactions between racial and regional disparities and other contributors is warranted.[Table: see text]